Investigation of bi-directional crosstalk between leukaemia and the cancer micro-environment (Rus...

Acute myeloid leukaemia (AML) is a cancer of the bone marrow (BM) microenvironment. Presently approximately 80% of patients diagnosed with AML will die of the disease, most within a year of diagnosis. Our group has recently defined novel pro-tumoral interactions between leukaemia cells and the non-malignant microenvironment cells that surround them which promote AML survival, proliferation and chemotherapy resistance. In this research project we hypothesise that the BM microenvironment of AML changes from a ‘non-diseased' BM phenotype to a definable pro-tumoural ‘diseased' BM phenotype. Moreover we propose that this phenotypic change within the non-malignant cells of the bone marrow is driven by the leukaemia and furthermore necessary for tumour survival. The detail of these changes are presently unknown. In addition it is also unknown at what stage of AML disease development do the BM microenvironment changes begin to occur and in which order. Therefore this project aims to use an in-vivo model of AML (already established in our lab (all necessary ethical and home office permissions in place) in which samples of primary AML taken from patients attending the Norfolk and Norwich University Hospital will be transplanted into immunocompromised NSG mice. We will then harvest the tissue from the BM of engrafted diseased animals at different time points post transplantation and then single cell sort the mesenchymal cells for single cell transcriptome analysis. It is envisaged that information generated from this descriptive research (phase 1 - years 1 and 2) will immediately lead to further hypothesis driven studies for the studentship investigating the essential components of the bi-directional crosstalk between AML and the cells in the surrounding micro-environment (phase 2 - years 2 and 3). Further forward and more broadly we expect the data generated from this work will define new therapeutic targets to treat AML.

Funding notes

This PhD project is jointly funded by the Faculty of Medicine and Health Sciences and the Earlham Institute funded studentship. This studentship is funded for 3 years and comprises home/EU fees, an annual stipend of £14,057 and £1000 per annum to support research training.